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Pain Control pp 119-143 | Cite as

The Role of the Endocannabinoid System in Pain

  • Stephen G. Woodhams
  • Devi Rani Sagar
  • James J. Burston
  • Victoria Chapman
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 227)

Abstract

Preparations of the Cannabis sativa plant have been used to analgesic effect for millenia, but only in recent decades has the endogenous system responsible for these effects been described. The endocannabinoid (EC) system is now known to be one of the key endogenous systems regulating pain sensation, with modulatory actions at all stages of pain processing pathways. The EC system is composed of two main cannabinoid receptors (CB1 and CB2) and two main classes of endogenous ligands or endocannabinoids (ECs). The receptors have distinct expression profiles, with CB1 receptors found at presynaptic sites throughout the peripheral and central nervous systems (PNS and CNS, respectively), whilst CB2 receptor is found principally (but not exclusively) on immune cells. The endocannabinoid ligands are lipid neurotransmitters belonging to either the N-acyl ethanolamine (NAEs) class, e.g. anandamide (AEA), or the monoacylglycerol class, e.g. 2-arachidonoyl glycerol (2-AG). Both classes are short-acting transmitter substances, being synthesised on demand and with signalling rapidly terminated by specific enzymes. ECs acting at CB1 negatively regulate neurotransmission throughout the nervous system, whilst those acting at CB2 regulate the activity of CNS immune cells. Signalling through both of these receptor subtypes has a role in normal nociceptive processing and also in the development resolution of acute pain states. In this chapter, we describe the general features of the EC system as related to pain and nociception and discuss the wealth of preclinical and clinical data involving targeting the EC system with focus on two areas of particular promise: modulation of 2-AG signalling via specific enzyme inhibitors and the role of spinal CB2 in chronic pain states.

Keywords

Pain Endocannabinoid Analgesia 

Abbreviations

2-AG

2-Arachidonoyl glycerol

Δ9-THC

Δ9-Tetrahydrocannabinol

ABHD6

αβ-Hydrolase domain 6

ABHD12

αβ-Hydrolase domain 12

ACC

Anterior cingulate cortex

AEA

Anandamide

AM251

A CB1 selective receptor inverse agonist/antagonist

CB1

Cannabinoid type 1 receptor

CB2

Cannabinoid type 2 receptor

CCI

Chronic constriction injury (neuropathic pain model)

CNS

Central nervous system

DAGLα

Diacylglycerol lipase-α

DRG

Dorsal root ganglia

EC

Endocannabinoid

FAAH

Fatty acid amide hydrolase

fMRI

Functional magnetic resonance imaging

GPCR

G protein-coupled receptor

MAG

Monoacylglycerol

MAGL

Monoacylglycerol lipase

NAE

N-acylethanolamine

NAPE-PLD

N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D

PAG

Periaqueductal grey matter

PKC

Protein kinase C

PNS

Peripheral nervous system

RVM

Rostral ventromedial medulla

SR144528

A CB2 selective receptor antagonist

TRPV1

Transient receptor potential vanilloid 1

WDR

Wide dynamic range neuron; a class of spinal neuron with key involvement in the transduction of nociceptive input

Notes

Acknowledgements

D.S. and J.J.B. are funded by Arthritis Research UK Pain Centre funding (grant no. 18769).

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Stephen G. Woodhams
    • 1
  • Devi Rani Sagar
    • 2
    • 3
  • James J. Burston
    • 2
    • 3
  • Victoria Chapman
    • 2
    • 3
  1. 1.Momentum Laboratory of Molecular NeurobiologyInstitute of Experimental Medicine, Hungarian Academy of SciencesBudapestHungary
  2. 2.Arthritis Research UK Pain CentreUniversity of NottinghamNottinghamUK
  3. 3.School of Life Sciences, Queen’s Medical CentreUniversity of NottinghamNottinghamUK

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